1. Field of the Invention
This invention relates to a method for fabricating an array pH sensor and a readout circuit of such array pH sensor, and more particularly to a method for fabricating an array pH sensor and a readout circuit of such array pH sensor by utilizing an extended gate ion sensitive field effect transistor (EGFET). The structure of this EGFET in combination with fabrication of biosensors and its readout circuit are produced as an integrated biosensor system. Therefore, the present invention can be applied to some applications such as medical detection, circuit design, semiconductor component fabrication, etc.
2. Description of the Prior Art
Conventional glass electrodes have many advantages such as high linearity, excellent ion selectivity and good stability. However, due to the relatively large volume, high cost and long reaction time, the technologies for fabricating these ion selective glass electrodes have been developed toward the technologies of established silicon semiconductor integrated circuits so as to fabricate field effect sensors. Thus, the conventional glass electrodes are replaced.
In 1970, Piet Bergveld P. in “Development of an ion-sensitive solid-state device for neurophysiological measurements”, IEEE Transaction Biomedical Engineering, BME-17, pp. 70-71, 1970, has firstly removed the metal portion from the gate electrode of a general metal oxide semiconductor field effect transistor (MOSFET). Then, the device is dipped into an aqueous solution. With the oxide layer of the sensor's gate electrode serving as an insulating ion sensing membrane, when the transistor is in contact with solutions with different pH values, different potential changes will occur at an interface between the transistor and the solution, such that the current passing through its channel is changed accordingly. In such manner, the pH values or concentrations of other ions can be measured. Thus, this device is referred by Piet Bergveld as a field effect ion sensor.
In 1970's, the studies and the applications of the field effect ion sensors were still under exploration. D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 1, pp. 57-62, 1990. However, in 1980's, the studies of the field effect ion sensors were promoted to a new level. The studies about those basic principle researches, crucial technologies or practical applications have been greatly progressed. For example, based on the structure of the ion sensitive field effect transistor, the types of field effect transistor fabricated for measuring a variety of ions and chemical substances had more than 20 or 30. In the aspects of miniaturization, module or multifunction, the component has been greatly developed. See also D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 6, pp. 52-60, 1991; D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 1, pp. 49-56, 1992; and D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 2, pp. 51-55, 1992.
The ion sensitive field effect transistor have been dominated all over the world with several decades of development, because they have the following special features, when compared with the conventional ion selective electrodes. They can be miniaturized to perform microanalysis of solutions. They have high input impedance but low output resistivity. D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 1, pp. 57-62, 1990.
Due to the above advantages, many research institutes have been interested in researching the ion sensitive field effect transistor since the past twenty years. Some important researches associated such sensors can be depicted as follows:
(1) miniaturization of reference electrodes (D. Yu, G. H. Wang, and S. X. Wu, Chemical Sensors, J. Sensor & Transducer Tech., No. 3, pp. 53-57, 1991);
(2) differential field effect ion sensor (Gui-Hua Wang, Dun Yu and Yao-Lin Wang, “ISFET temperature characteristics”, Sensors and Actuators, 11, pp. 221-237, 1987);
(3) field effect ion sensors having immobile enzyme for detecting function information of organisms, for example glucose concentration, oxygen content in blood, etc. (A. Saito, S. Miyamoto, J. Kimura, T. Kuriyama, “ISFET glucose sensor for undiluted serum sample measurement”, Sensors and Actuators B, 5, pp. 237-239, 1992);
(4) exploration of theories, for example adsorptive bonding models;
(5) researches on packaging materials (R. E. G. van Hal, “Characterization and testing of polymer-oxide adhesion to improve the packaging reliability of ISFETs”, Sensors and Actuators B, 23, pp. 17-26, 1995);
(6) integration of measurement systems and sensors (B. H. Van Der Schoot, H. H. Van Den Vlekkert, N. F. De Rooij, A Van Den Berg and A. Grisel, “A flow injection analysis system with glass-bonded ISFETs for the simultaneous detection of calcium and potassium ion and pH”, Sensors and Actuators B, 4, pp. 239-241, 1991); and
(7) researches on simulation of field effect ion sensors (M. Grattarola, “Modeling H+-sensitive FETs with spice”, IEEE Transactions on Electron Devices, Vol. 39, NO. 4, pp. 813-819, April 1992).
The extended gate ion sensitive field effect transistor (EGFET) is one of an ion sensitive field effect transistor and firstly introduced by J. Spiegel (J. Van Der Spiegel, I. Lauks, P. Chan, and D. Babic, “The extended gate chemical sensitive field effect transistor as multi-species microprobe”, Sensors and Actuators, 4, pp. 291-298, 1983). In contrast to the traditional ion sensitive field effect transistor, the extended gate field effect transistor retains the original metal gate of the metal-insulation layer-semiconductor transistor and the sensitive membrane is deposited on the other end extended from the metal gate. Comparing with the traditional ion sensitive field effect transistor, the extended gate ion sensitive field effect transistor has a lot of advantages, for example (1) the conducting line provides electrostatic protection for the sensor; (2) the transistor of the sensor can prevent direct contact with the aqueous solution; and (3) the influence of light on the sensor is reduced.
The first publication associated to the EGFET is disclosed in 1983 (J. Van Der Spiegel, I. Lauks, P. Chan, and D. Babic, “The extended gate chemical sensitive field effect transistor as multi-species microprobe”, Sensors and Actuators, 4, pp. 291-298, 1983). However, the papers published on the international journals are insufficient. After 1986, few researchers published the papers associated to EGFET. Until 1988, our research group proposed an improved EGFET structure, which is divided into two portions, i.e. a sensing portion of SnO2/Al/SiO2 and a readout circuit portion. L. L. Chi, J. C. Chou, W. Y. Chung, T. P. Sun and S. K. Hsiung, “Study on extended gate field effect transistor with tin oxide sensing membrane”, Material Chemistry and Physics, 63 (2000) 19-23.
[14] L. L. Chi, L. T. Yin, J. C. Chou, W. Y. Chung, T. P. Sun, K. P. Hsiung and S. K. Hsiung, “Study on separative structure of EnFET to detect acetylcholine”, Sensors and Actuators B, 71, pp. 68-72, 2000.
The patents related to the ISFET are listed hereinafter.
U.S. Patent Publication No. 5,833,824, inventor: Barry W. Benton, date of patent: Nov. 10, 1998, entitled “Dorsal substrate guarded ISFET sensor” disclosed an ion sensitive field effect transistor (ISFET) sensor for sensing ion activity of a solution, wherein the sensor includes a substrate and an ion sensitive field effect transistor. The substrate has a front surface exposed to the solution, a back surface opposite to the front surface and an aperture extending between the front and back surfaces. This patent connects the back surface of the substrate to the front-end sensor through the aperture surface such that only the back surface region is exposed to the solution.
In this study, the word “extended ISFET” and “extended-gate field effect transistor (EGFET)” indicates the same thing. The chemical sensors referenced in this paper were based on the ion sensitive field effect transistors (ISFETs), which were first reported by P. Bergveld [1]. However, the structure of the sensor in the present invention were based on the extended-gate field effect transistor (EGFET), which was first introduced by Van Der Spiegel et al. [2]. The extended-gate filed effect transistor differs from the ISFET in that it was separated into two parts; one was a sensing structure containing a sensitive membrane; the other was a MOSFET structure. The configuration of the extended-gate field effect transistor has several advantages: firstly, it has a lower cost than traditional ion-sensitive field effect transistor; secondly, the transistor could be tested and characterized without the need to contact solutions; thirdly, the device could avoid the influences of temperature and light. The conditions of the disposable biosensor were mass-production and low-cost. Therefore, the extended-gate configuration is useful to develop disposable biosensors for clinical applications.
U.S. Patent Publication No. 6,353,323, inventor: Fuggle; Graham Anthony, Date of patent: Mar. 5, 2002, entitled “Ion concentration and pH measurement” discloses an apparatus and a measuring method for processing the front-end sensor. The front-end ion sensor comprises an ion selective electrode, a reference electrode and an ion sensitive field effect transistor, all of which are immersed in the solution. The sensor is connected to the pre-amplifier, and the reference electrode is connected to the readout circuit so as to separate the sensor from the reference electrode. Accordingly, plural sensor can use a common reference electrode.
U.S. Patent Publication No. 5,350,701, inventor: Jaffrezic-Renault; Nicole; Chovelon; Jean-Marc; Perrot; Hubert; Le Perchec; Pierre; Chevalier; Yves, Date of patent: Sep. 27, 1999, entitled “Process for producing a surface gate of an integrated electrochemical sensor, consisting of a field-effect transistor sensitive to alkaline-earth species and sensor obtained” discloses an improved production process for treating a surface gate comprising a selective membrane as an integrated chemical sensor. A layer of chemically synthesized phosphonate-based is deposited on the gate region of the field-effect ion sensor, and thus the sensing membrane is reactive to alkaline-earth species. This sensor is effective as a detector for measuring concentration of alkaline-earth species, in particular the calcium ion.
U.S. Patent Publication No. 5,319,226, inventor: Sohn; Byung K.; Kwon; Dae H., Date of patent: Jun. 7, 1994, entitled “Method of fabricating an ion sensitive field effect transistor with a Ta2O5 hydrogen ion sensing membrane” discloses a radio frequency sputtering method for depositing a tantalum oxide film onto a non-conducting silicon nitride film, i.e. onto the gate region of the ion sensor, thereby forming a field-effect ion sensor having the tantalum oxide/silicon nitride/silicon dioxide. The Ta2O5film has a thickness of from 40×10−9 to 50×10−9 m. Then, the resultant film is annealed at an elevated temperature of 375° C. to 450° C. in oxygen gas ambience for about one hour.
U.S. Patent Publication No. 4,657,658, inventor: Sibbald; Alastair, Date of patent: Apr. 14, 1987, entitled “Semiconductor devices” uses a semiconductor integrated circuit for sensing a physico-chemical property of an ambient. The circuit includes a pair of semiconductor devices having a similar geometric and physical structure. Its readout circuits are connected to the same circuit, and the overall structure thereof comprises a metal oxide semiconductor field effect transistor and a field-effect ion sensor so as to construct a differential module system.
U.S. Patent Publication No. 5,922,183, inventor: Rauh; R. David, Date of patent: Jul. 13, 1999, entitled “Metal oxide matrix biosensors” uses a metal oxide-based film as substrate of biological molecules. Such configuration is suitable for developing electrochemical biosensors. The most common metal oxide-based film is a hydrous metal oxide, which can be conductive or semiconductor and have excellent stability against dissolution or irreversible reaction in aqueous and non-aqueous solutions. The metal oxide can be used for both amperometric and potentiometric sensing of enzymes, antibodies, antigens, DNA strands, etc. Iridium oxide is the preferred embodiment of metal oxide film due to the best sensing feature. Furthermore, some other metals, for example Ru, Ti, Pd, Pt, Zr, etc., have similar features and their oxides are very stable against oxidation damage.
The hydrogen ion sensing membrane commonly used on the gate oxide of the field-effect ion sensitive transistor can be selected from silicon dioxide, silicon nitride, tantalum oxide, aluminum oxide, etc., for example. A field-effect ion sensitive transistor with having a hydrogen ion sensing membrane made of tin dioxide is first fabricated in the laboratory. H. K. Liao, J. C. Chou, W. Y. Chung, T. P. Sun and S. K. Hsiung, “Study on the interface trap density of the SiN4/SiO2 gate ISFET”, Proceedings of the 3rd East Asian Conference on Chemical Sensors, Seoul, Korea, November 5-6, pp. 340-400, 1997. The characteristics of this field-effect ion sensitive transistor has an approximate Nernst response in a range of from 56 to 58 mV/pH, a high linear sensitivity, a long-termed stability with low drift, and a low response time of <0.1 second. In addition, the temperature of this sensor can be reduced to zero at an appropriate working current.
Since the ion sensitive field-effect transistor can be used to fabricate array ion sensor array pH sensor by means of the semiconductor fabrication process, the sampling number for detection of the sensor will be increased. The error resulting from one single sensing device can be decreased due to the larger sampling number signals. Thus, when the array sensor is used to measure hydrogen concentration in a human body, the result has a high accuracy and a low error so as to enhance its measuring performance. Furthermore, since the ion sensitive field-effect transistor can be miniaturized, the amount of body fluid to be draw out will be minimized for microanalysis. Due to the rapid reaction time of the ion sensitive field-effect transistor, the array sensor can instantaneously monitor the solution to be measured, thereby reducing measuring time of the tested sample.
Accordingly, the above-described prior art product is not a perfect design and has still many disadvantages to be solved.
In views of the above-described disadvantages resulted from the prior art, the applicant keeps on carving unflaggingly to develop method for fabricating an array pH sensor and a readout circuit device of such array pH sensor according to the present invention through wholehearted experience and research.